Division of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan.
Department of Nephrology and Hypertension, Kawasaki Medical School, Okayama, Japan.
J Hum Genet. 2023 Feb;68(2):55-64. doi: 10.1038/s10038-022-01094-1. Epub 2022 Nov 21.
Chronic kidney disease (CKD) is a syndrome characterized by a gradual loss of kidney function with decreased estimated glomerular filtration rate (eGFR), which may be accompanied by an increase in the urine albumin-to-creatinine ratio (UACR). Although trans-ethnic genome-wide association studies (GWASs) have been conducted for kidney-related traits, there have been few analyses in the Japanese population, especially for the UACR trait. In this study, we conducted a GWAS to identify loci related to multiple kidney-related traits in Japanese individuals. First, to detect loci associated with CKD, eGFR, and UACR, we performed separate GWASs with the following two datasets: 475 cases of CKD diagnosed at seven university hospitals and 3471 healthy subjects (dataset 1) and 3664 cases of CKD-suspected individuals with eGFR <60 ml/min/1.73 m or urinary protein ≥ 1+ and 5952 healthy subjects (dataset 2). Second, we performed a meta-analysis between these two datasets and detected the following associated loci: 10 loci for CKD, 9 loci for eGFR, and 22 loci for UACR. Among the loci detected, 22 have never been reported previously. Half of the significant loci for CKD were shared with those for eGFR, whereas most of the loci associated with UACR were different from those associated with CKD or eGFR. The GWAS of the Japanese population identified novel genetic components that were not previously detected. The results also suggest that the group primarily characterized by increased UACR possessed genetically different features from the group characterized by decreased eGFR.
慢性肾脏病（CKD）是一种以肾小球滤过率（eGFR）逐渐下降为特征的综合征，可能伴有尿白蛋白与肌酐比值（UACR）升高。虽然已经对与肾脏相关的特征进行了跨种族全基因组关联研究（GWAS），但在日本人群中进行的分析很少，特别是对于 UACR 特征。在这项研究中，我们进行了 GWAS，以确定与日本个体多种肾脏相关特征相关的基因座。首先，为了检测与 CKD、eGFR 和 UACR 相关的基因座，我们使用以下两个数据集分别进行了 GWAS：7 所大学医院诊断的 475 例 CKD 患者和 3471 例健康受试者（数据集 1）以及 3664 例 eGFR<60ml/min/1.73m 或尿蛋白≥1+的疑似 CKD 患者和 5952 例健康受试者（数据集 2）。其次，我们对这两个数据集进行了荟萃分析，并检测到以下相关基因座：10 个与 CKD 相关的基因座、9 个与 eGFR 相关的基因座和 22 个与 UACR 相关的基因座。在所检测到的基因座中，有 22 个以前从未报道过。CKD 的显著基因座中有一半与 eGFR 共享，而与 UACR 相关的大多数基因座与与 CKD 或 eGFR 相关的基因座不同。日本人群的 GWAS 确定了以前未检测到的新的遗传成分。这些结果还表明，主要以 UACR 升高为特征的组与以 eGFR 降低为特征的组具有遗传上不同的特征。
